Process for the preparation of N-substituted pyrazole compounds

Abstract

A process for the preparation of a compound of formula I: wherein, R 1 represents hydrogen, cyano, nitro, halogen, or acyl; R 2 represents aryl, alkenyl, alkynyl, halogen substituted alkyl, halogen substituted alkenyl, or halogen substituted alkynyl; R 3 represents hydrogen or NR 6 R 7 wherein R 6 and R 7 each independently represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R 6 and R 7 together with, the N atom attached form a heterocycle; and R 4 represents hydrogen, alkyl, aryl, or heteroaryl; the process including oxidizing a compound of formula II:

The invention claimed is: 
     
       1. A process for the preparation of a compound of formula I: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  represents hydrogen, cyano, nitro, halogen, or acyl; 
         R 2  represents alkyl, alkenyl, alkynyl, halogen substituted alkyl, halogen substituted alkenyl, or halogen substituted alkynyl; 
         R 3  represents hydrogen or NR 6 R 7  wherein R 6  and R 7  each independently represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R 6  and R 7  together with the N atom attached form a heterocycle; and 
         R 4  represents hydrogen, alkyl, aryl, or heteroaryl; 
         said process comprising oxidizing a compound of formula II: 
       
       
         
           
           
               
               
           
         
         with an oxidant in the absence of trifluoroperacetic acid and in the presence of a catalyst comprising sodium tungstate and hydrochloric acid. 
       
     
     
       2. The process according to  claim 1 , wherein R 1  is cyano. 
     
     
       3. The process according to  claim 1 , wherein R 2  is C 1  to C 4  alkyl, C 2  to C 4  alkenyl, C 2  to C 4  alkynyl, C 1  to C 4  halogen substituted alkyl, C 2  to C 4  halogen substituted alkenyl, or C 2  to C 4  halogen substituted alkynyl. 
     
     
       4. The process according to  claim 3 , wherein R 2  is trifluoromethyl. 
     
     
       5. The process according to  claim 1 , wherein R 3  is NR 6 R 7  and R 6  and R 7  each independently represent hydrogen or C 1  to C 4  alkyl. 
     
     
       6. The process according to  claim 1 , wherein R 4  is an optionally substituted phenyl moiety. 
     
     
       7. The process according to  claim 1 , wherein the compound of formula I is a compound of formula IV: 
       
         
           
           
               
               
           
         
         wherein R 9 , R 10  each independently represent halogen; and 
         R 11  represents alkyl, alkenyl, alkynyl, halogen substituted alkyl, halogen substituted alkenyl, or halogen substituted alkynyl; 
         and the compound of formula II is a compound of formula V: 
       
       
         
           
           
               
               
           
         
       
     
     
       8. The process according to  claim 7 , wherein R 9  and R 10  are both chlorine. 
     
     
       9. The process according to  claim 7 , wherein R 11  is trifluoromethyl or C 1  to C 6  alkyl. 
     
     
       10. The process according to  claim 7 , wherein the compound of formula IV is 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethyl sulphinyl pyrazole. 
     
     
       11. The process according to  claim 1 , wherein the process is carried out at a temperature in the range of 0 to 10° C. 
     
     
       12. The process according to  claim 11 , wherein the temperature is in the range of 5 to 8° C. 
     
     
       13. The process according to  claim 1 , wherein the oxidation is carried out in the presence of an organic solvent. 
     
     
       14. The process according to  claim 13 , wherein the organic solvent comprises ethylene dichloride. 
     
     
       15. The process according to  claim 1 , wherein the oxidant comprises a quinone, a peroxide, a hypohalite, or an alkali metal hydroxide. 
     
     
       16. The process according to  claim 15 , wherein the oxidant comprises hydrogen peroxide. 
     
     
       17. The process according to  claim 16 , wherein hydrogen peroxide is the sole oxidant. 
     
     
       18. The process according to  claim 1 , wherein the molar ratio of oxidant to the compound of general formula II is from 0.1 to 10. 
     
     
       19. The process according to  claim 18 , wherein the molar ratio of oxidant to the compound of general formula II is from 0.5 to 5. 
     
     
       20. The process according to  claim 19 , wherein the molar ratio of oxidant to the compound of general formula II is from 1.1 to 1.7. 
     
     
       21. A process for preparation of a compound of formula IV according to  claim 7 , which further comprises reacting CF 3 SCl with a compound of formula VI to produce a compound of formula V according to step A below; and the oxidizing comprises reacting an oxidant with a compound of formula V in a medium comprising substantially no trifluoroperacetic acid and in the presence of a catalyst comprising sodium tungstate and hydrochloric acid to produce a compound of formula IV, according to step B of the reaction scheme below: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  represents hydrogen, cyano, nitro, halogen, or acyl; 
         R 2  represents trifluoromethyl; 
         R 3  represents hydrogen or NR 6 R 7  wherein R 6  and R 7  each independently represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R 6  and R 7  together with the N atom attached form a heterocycle; 
         R 9 , R 10  each independently represent a halogen; and 
         R 11  represents alkyl, alkenyl, alkynyl, halogen substituted alkyl, halogen substituted alkenyl, or halogen substituted alkynyl. 
       
     
     
       22. A process for preparation of a compound of formula V, which comprises step A: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  represents hydrogen, cyano, nitro, halogen, or acyl; 
         R 2  represents trifluoromethyl; 
         R 3  represents hydrogen or NR 6 R 7  wherein R 6  and R 7  each independently represent hydrogen, alkyl, alkenylalkyl, alkynylalkyl, formyl, optionally halogen substituted alkanoyl, optionally halogen substituted alkoxycarbonyl, or alkoxymethyleneamino, halogen, or R 6  and R 7  together with the N atom attached form a heterocycle; 
         R 9 , R 10  each independently represent a halogen; and 
         R 11  represents alkyl, alkenyl, alkynyl, halogen substituted alkyl, halogen substituted alkenyl, or halogen substituted alkynyl. 
       
     
     
       23. The process according to  claim 22 , wherein R 1  represents C 1 -C 4  acyl.